544:
myophosphorylase. The resulting excess of glucose is metabolized down to lactic acid (the body cannot increase aerobic metabolism in an instant), recharging all AMP to ATP. The lactate is dumped back into blood and urine. The higher the glycemic index of the food is, the greater proportion of carbohydrates (and calories) is wasted into urine. If the person is at rest at this moment, and pays attention, a sudden increase in the breathing frequency due to lactate dumping is readily observable. If the rise in the blood lactate is particularly sharp, and the person happened to be breathing slowly, a heart palpitation may sometimes be observable. The lactic acidosis with palpitation may also occur during sleep, if stomach emptying has been delayed e.g. due to digestion requirements of the food or its high volume, and the person went to sleep before absorption has started. In this case the person will be awaken in a state of distress, with rapid breathing. The person may recall seeing a nightmare. Delayed stomach emptying creates especially favorable conditions for the shock lactic acidosis, because the digestive system may meanwhile still inhibit fatty acid release and oxidation, helping more muscles to run out of glycogen in those persons, who are otherwise still able to maintain its stores between meals. It has been experimentally demonstrated, that delayed gastric emptying prolongs the duration of the GLP-1 signal.
500:
acid cycle to be sped up by some other mechanism (perhaps by the allosteric mechanism that reacts to the lower concentration of ATP, or by amplification of the residual AMPD activity by the bloated AMP pool), until ATP production is balanced with ATP consumption. AMP conversion to adenosine, excretion to the blood (as AMP and its various metabolites), further conversion to uric acid and excretion to urine becomes significant for some time, until all AMP is eliminated from the muscle cell. The muscle movements become noticeably less precise. Breathing slows down, and from this moment reacts very weakly to the load and not at all to the perceived effort. It becomes hard to rapidly increase the load on a muscle, as in McArdle's disease, and such a rapid load increase will dump even more purines into blood and urine (looking like translucent or rust-colored sharp shiny crystals and being highly irritating). The same situation would occur if blood flow to muscle cells becomes insufficient (except that somewhat less AMP is spilled over, and somewhat more of it is metabolized inside the muscle cell). On the other hand, there will be no lasting muscle pain from lactate, and continuous aerobic activity is possible. Oxidation of odd-numbered saturated fatty acids may provide another mechanism, although very gradual, to up-regulate citric acid cycle during exercise.
532:
stomach and before bulk absorption occurs, when continuous exercise becomes very hard, and easily triggers rhabdomyolysis. It probably happens because the digestive system senses and signals forthcoming delivery of sugars, inhibiting fatty acid release and oxidation, and starving glycogen-less muscle cells of the sole available source of energy. Even simple continuous exercise, like walking or washing dishes by hand right after the meal, may trigger rhabdomyolysis in the exercising muscles. This rhabdomyolysis is probably not of exertional, but of hypoglycemic nature, as loaded glycogen-less muscles can rapidly remove glucose from blood, and the normal mechanism of glucose homeostasis lacks the required responsiveness or capacity to prevent hypoglycemia. The broken down myocytes probably do not yield much glucose. Unlike the case with exertional rhabdomyolysis, there is no warning. At rest, however, the liver will effortlessly cover the whole body energy needs until absorption of carbohydrates occurs.
468:
myophosphorylase, which will start liberating glucose from glycogen and make it available to the glycolytic pathway, producing pyruvate and recharging AMP back to ATP. Due to the greater availability of pyruvate as a substrate, and pyruvate also contributing a citric acid cycle intermediate, α-ketoglutarate, while consuming glutamate, the citric acid cycle will also speed up. The combination of glycolysis and the citric acid cycle now balances ATP production with ATP demand and the pool of AMP does not grow further. Because all pyruvate is not burned down in the citric acid cycle—a consequence of the pyruvate's concentration regulating its burning at this moment—the excess is converted to lactate and passed into blood as lactic acid.
504:
In McArdle's, the highly active AMP deaminase, which additionally experiences amplification from the bloated AMP pool due to the lack of the moderating effect of myophosphorylase, is able to produce a readily observable "second wind" phenomenon almost exactly 7 minutes after a significant load increment. In AMPD deficiency, glycogen-less muscles will feel mostly the same by the time they become able to take another load increment. A load decrement may produce some sense of relief, though, if the pool of the citric acid cycle intermediates built up so far is sufficient to maintain full purine nucleotide energy charge at the lower load.
524:
also indirectly affect other organs. There is little or no warning for nearing toxicity, because the purine nucleotide energy charge is still relatively high, the leg muscles do not cramp, and remain functional. In contrast, while muscle glycogen is available, accumulation of lactic acid in this situation would produce a noticeable sensation. On the other hand, in persons with balanced AMPD and myophosphorylase activities in muscle cells, lactic acid and ammonia are produced simultaneously, counteracting each other's effects to some degree.
496:
muscle cells cannot take up glucose from blood, due to myophosphorylase maintaining a higher concentration of it inside loaded cells, and if liver has already filled its glycogen stores up to capacity. So, ultimately, in this state, working muscle cells are destined to lose all glycogen. AMP breakdown to adenosine in this state is minor, because the pool of AMP is kept small by the vigorous regulatory action of myophosphorylase. Maximum continuous exertion is limited by the onset of burning sensation from lactate accumulation in muscles.
480:
re-absorption threshold (5–6 mmol/L in general population), it gets lost to urine, wasting many calories (and producing bright matte yellow particles on surfaces where urine dries). At about the same time the kidney will also start correcting blood acidity by acidifying urine. Overly acidic urine causes irritation that feels like a frequent urge to urinate (with little volume) and a "hot" urine.
429:. Though the body can manufacture some ribose and obtain more from RNA-rich sources such as beans and red meat, this loss of ribose due to MADD is sometimes sufficient to create a shortage in the body, resulting in symptoms of severe fatigue and muscle pain. This outcome is especially likely if the individual regularly exercises vigorously or works physically over a period of weeks or months.
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207:. MADD causes an increase of free adenosine during heavy activity which may cause exercise-induced muscle pain. Over time, excess free adenosine down-regulates primary A1 adenosine receptors, leading to increased muscle pain. Secondary receptors (A3) increase peripheral inflammation, which also increases pain.
146:("A;A") has also been identified. While there has been no consensus on the effects of the heterozygous form – either "C;T" or "A;G" – some evidence has been found that it too has caused AMPD1 deficiency. In addition, some sources have suggested the existence of a rare, acquired form of AMPD1 deficiency.
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The following is a very simplified model of what may be going on inside a muscle cell with AMPD deficiency. There are two major semi-stable states: one with intra-cellular glycogen available, and one with glycogen exhausted. Both states are modified by how much the citric acid cycle is down-regulated
325:
During heavy or prolonged mild to moderate activity, other enzymes convert two molecules of ADP into one ATP molecule and one AMP molecule, making more ATP available to supply energy. AMP is normally converted into IMP by myoadenylate deaminase—so myoadenylate deaminase deficiency reduces energy that
870:
Fredholm, B. B.; Halldner, L.; Johansson, C.; Schulte, G.; Lövdahl, C.; Thorén, P.; Dunwiddie, T. V.; Masino, S. A.; Poelchen, W.; Diao, L.; Illes, P.; Zahniser, N. R.; Valen, G.; Tokuno, S.; Sommerschild, H.; Giménez-Llort, L.; Fernández-Teruel, A.; Escorihuela, R. M.; Wiesenfeld-Hallin, Z.; Xu, X.
483:
In order to excrete lactate, kidney must also excrete magnesium as an obligatory cation, which may lead to acute and chronic magnesium deficiency. Supplementary magnesium in the form of lactate or citrate may be rapidly lost in the same way. Because magnesium is essential to aerobic metabolism, over
543:
When a carbohydrate-rich food has been eaten before AMP has been eliminated from muscle cells, when bulk absorption starts, plenty of glucose becomes available in the blood, is taken up by muscle cells, is added to the glycogen store, but then immediately becomes liberated by the still up-regulated
503:
As the short-term regulation of ATP production becomes very weak after the exhaustion of glycogen, the medium-term regulation becomes enabled, but with a progressively weaker authority at higher purine nucleotide energy charge levels, which causes some differences in symptoms compared to McArdle's.
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Eventually, all glycogen is exhausted, and the muscle cell enters another semi-stable state. During this transition, up-regulation of the citric acid cycle due to abundance of pyruvate is reversed, and a substantial part of the ATP pool is necessarily discharged down to AMP, which allows the citric
491:
In order to keep the excreted metabolites in solution, the kidney also has to excrete water. This is in contrast to complete oxidation of lactic acid, which would actually yield metabolic water for the body. This may lead to onset of acute thirst some tens of minutes into exercise in this state, if
475:
In muscle cells with AMPD deficiency, ATP production rate of the citric acid cycle will not be synchronized with ATP demand. It was demonstrated, that muscle cells, that lack AMPD1, stock and consume significantly more glutamate, and produce more alanine in this state, compared to healthy controls,
181:
Without myoadenylate deaminase, heavy activity causes adenosine to be released into the cell or perfused into the surrounding tissues. Fatigue and sedation after heavy exertion can be caused by excess adenosine in the cells which signals muscle fiber to feel fatigued. In the brain, excess adenosine
523:
If the person keeps standing still for longer, rather than restoring circulation in the leg muscles (e.g. by sitting down, walking, or cycling), the ammonia, produced by the amplified residual AMPD activity, may accumulate in the muscle cells and in the surrounding tissues to toxic levels, and may
519:
In case of leg muscles, where circulation is substantially dependent on their cyclical contraction when the body is upright, a small but useful degree of initial up-regulation of the citric acid cycle may be achieved just by standing still for a few minutes. It is most useful when a long period of
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Most of the AMP probably spills into blood unchanged, and is gradually returned to the muscle cell, if its concentration there falls due to gradual recharge to ATP. The blood thus plays a role of a big AMP buffer. Idle muscles may also take up some free AMP. The spillover also limits, how much the
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If the muscle load is small, lactate is mostly recycled back into glucose or burned by other cells in the body. However the newly generated glucose is made available to all cells in the body, not just to muscle cells. The ability of the body to assimilate lactate may also be diminished, if working
471:
In muscle cells with normal AMPD activity, the purine nucleotide cycle would now start to gradually add fumarate to the pool of the citric acid cycle intermediates. This would decrease the excess rate of pyruvate production by increasing its consumption, increase the rate of AMP recharge to ATP by
557:
It may be especially important to have adequate dietary iodine in the glycogen-less state, so that stomach emptying is not excessively delayed, the up-regulation of the citric acid cycle in muscle cells in response to a load increment is not too slow, and the muscles can each time accept a bigger
511:
at this point, assuming the muscle cell is otherwise healthy. Adenosine production and lack of ammonia overproduction seem to strongly suppress rhabdomyolysis down to the purine nucleotide energy charge level, where the cell is able to signal pain, or where individual muscle fibers start cramping
587:
orally at a dose of approximately 10 grams per 100 pounds (0.2 g/kg) of body weight per day, and exercise modulation as appropriate. Taken hourly, ribose provides a direct but limited source of energy for the cells. Patients with myoadenylate deaminase deficiency do not retain ribose during
566:
The diagnosis of MADD needs to be considered in patients who have exercise induced myalgia, cramps and sometimes weakness. A mildly elevated creatine kinase may also occur. Exclusion of other muscular diseases such as McArdle's
Disease and carnitine cycle abnormalities should occur. MADD may be
531:
If a food containing even small but perceivable amount of sugar (simple sugars or disaccharides that can be tasted sweet, or starch that is at least minimally hydrolyzed by salivary amylase, or even some non-sugar sweeteners) is eaten in this state, there may be a period of time after it enters
479:
This state can last for as long as glycogen is available, and can be prolonged by constantly eating carbohydrate-rich food. If the load on muscles is greater than the body's ability to recycle lactate back into glucose, lactate will start to build up in the blood. Once lactate reaches its renal
487:
Although probably unrelated to AMPD deficiency, if the person happens to have a high load of d-lactate in the blood (mostly from food and colonic fermentation), the precipitate, the lactate loss and the magnesium loss may occur even before l-lactate (mostly from muscles) reaches its renal
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If the carbohydrate meal consists of a food (which doesn't need to be carbohydrate itself), that requires prolonged vigorous chewing, and then some time to be digested, for instance parboiled long grain rice, chewing may suddenly become very slow and difficult halfway through the meal.
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Start from the state where glycogen is available and the citric acid cycle is severely down-regulated. Once the cell has received a non-trivial load, and has expended the phosphocreatine reserve, a small quantity of ATP will become discharged down to AMP. AMP will instantly up-regulate
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residual AMPD activity can be amplified in this state. Thus, it may take the residual AMPD activity less time to build up citric acid cycle intermediates, when the whole body is warmed up for an exercise at the same time, rather than a specific group of muscles needed in the exercise.
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If a large group of muscles is still actively drawing fuels from blood after the most recent continuous exercise, in order to replenish the ATP and the phosphocreatine reserve, it may become sour without any additional exercise by the time the carbohydrate meal is finished.
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Muscle pain from MADD is not well understood, but is partially due to high levels of lactate. Increased levels of free adenosine temporarily decrease pain, allowing over-exertion without awareness. The over exertion can cause mild to severe cases of rhabdomyolysis, which is
949:
Vladutiu, Georgirene D.; Simmons, Zachary; Isackson, Paul J.; Tarnopolsky, Mark; Peltier, Wendy L.; Barboi, Alexandru C.; Sripathi, Naganand; Wortmann, Robert L.; Phillips, Paul S. (2006). "Genetic risk factors associated with lipid-lowering drug-induced myopathies".
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If carbohydrate-rich food is not consumed in this state, AMP elimination from the cell eventually completes, glycogen stores can be replenished again, and the cell transitions back to the original state but with reduced ATP pool and an up-regulated citric acid cycle.
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It is important for MADD patients to maintain strength and fitness without exercising or working to exhaustion. Learning this balance may be more difficult than normally, as muscle pain and fatigue may be perceived differently from normal individuals.
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Some seldom used but strong voluntary muscles, such as those involved in "pushing" during the act of defecation, are not tuned for aerobic mode, and may dump plenty of purines during their short work routine, if it happens in this state.
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Zöllner, N.; Reiter, S.; Gross, M.; Pongratz, D.; Reimers, C. D.; Gerbitz, K.; Paetzke, I.; Deufel, T.; Hübner, G. (1986). "Myoadenylate deaminase deficiency: Successful symptomatic therapy by high dose oral administration of ribose".
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the AMP molecules has three major effects. First, significant amounts of AMP are lost from the cell and the body. Second, ammonia is not freed when the cell does work. Third, the level of IMP in the cell is not maintained.
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Muscle weakness is not a major symptom, though the progressive effects of chronic muscle damage from rhabdomyolysis will eventually cause significant weakness. Similarly, the long-term metabolic effects may result in nerve
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re-absorption threshold. This happens because l-lactate and d-lactate compete with each other for renal re-absorption, and because d-lactate has a significantly lower renal re-absorption threshold, <1 mmol/L.
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which indicates occurrence of a higher concentration of pyruvate in the cell during exercise. The pool of AMP also grows bigger than in the controls, which would cause higher rate of glucose liberation from glycogen.
993:
Vockley, Jerry; Rinaldo, Piero; Bennett, Michael J.; Matern, Dietrich; Vladutiu, Georgirene D. (2000). "Synergistic
Heterozygosity: Disease Resulting from Multiple Partial Defects in One or More Metabolic Pathways".
871:
J.; Hårdemark, A.; Herlenius, E.; Pekny, M.; Gebré-Medhin, S.; Brown, R.; Ollerstam, A.; Persson, A. E. G.; Skøtt, O.; Johansson, B. R. (2003). "Consequences of eliminating adenosine A1 receptors in mice".
256:, an uncontrolled increase in body temperature, and permanent muscle damage in patients with MADD. Individuals with MADD are advised to notify their anesthesiologist about their condition prior to surgery.
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could also be helpful for AMPD patients, as it provides an alternative source of energy for anaerobic muscle tissue and was found to be helpful in the treatment of other, unrelated muscular myopathies.
512:(fail to relax from contraction in sync with the rest of the muscle), or the whole muscle fails to contract (when walking quickly downhill), allowing the person to appropriately modulate the exertion.
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Fischer, H.; Esbjornsson, M.; Sabina, R. L.; Stromberg, A.; Peyrard-Janvid, M.; Norman, B. (2007). "AMP deaminase deficiency is associated with lower sprint cycling performance in healthy subjects".
330:. Instead of being converted to IMP, the AMP builds up in the cells of affected individuals, spills into the blood, and is eventually metabolized in the liver. In persons with a defective enzyme,
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Notably, a small quantity of dietary fructose does not produce this effect (the lactic acidosis), as it is captured by liver and may be fully expended for replenishing liver glycogen.
157:(IMP). While the deficiency affects approximately 1–2% of people in populations of predominantly European descent, the disorder appears to be considerably rarer in Asian populations.
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189:, which is the rapid breakdown of muscle fibers, time to recovery is dependent on duration and intensity of original activity plus any excess activity during the recovery period.
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time, magnesium loss may lead to a vicious cycle, where the citric acid cycle is further down-regulated, lactate production is increased, and magnesium loss is increased again.
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the citric acid cycle, and consequently reduce liberation of glucose from glycogen, until increased supply of blood-borne fuels allows to shut down glycogenolysis completely.
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Wagner, D.R.; Gresser, U.; Zöllner, N. (1991). "Effects of Oral Ribose on Muscle
Metabolism during Bicycle Ergometer in AMPD-Deficient Patients".
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In most cases where myopathy is present with MADD, a second muscle disease is present and symptoms are worse than either disease in isolation.
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Once all AMP has been recharged to ATP, and glycogen stores allowed to replenish, the cell transitions back to the unmodified original state.
1446:
1325:
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919:
1218:
Sabina, Richard L.; Swain, Judith L.; Patten, Bernard M.; Ashizawa, Tetsuo; O'Brien, William E.; Holmes, Edward W. (1 December 1980).
1066:"Myoadenylate deaminase deficiency. Functional and metabolic abnormalities associated with disruption of the purine nucleotide cycle"
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1029:
Sabina, Richard L. (2000). "MYOADENYLATE DEAMINASE DEFICIENCY: A Common
Inherited Defect with Heterogeneous Clinical Presentation".
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637:
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removes the ribose and phosphorus from AMP, increasing levels of adenosine measured in muscle cells by ~16–25×, after exercise.
1269:"The effects of fiber enrichment of pasta and fat content on gastric emptying, GLP-1, glucose, and insulin responses to a meal"
1737:
796:
641:
103:
906:
Blazev R, Lamb GD (December 1999). "Adenosine inhibits depolarization-induced Ca(2+) release in mammalian skeletal muscle".
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The third effect, the reduction in IMP, is also not well understood. It may somehow result in a reduction in the amount of
823:"Repeated Dosing with Oral Allosteric Modulator of Adenosine A1 Receptor Produces Tolerance in Rats with Neuropathic Pain"
737:"Systemic Adenosine Infusion Alleviates Spontaneous and Stimulus Evoked Pain in Patients with Peripheral Neuropathic Pain"
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identified if there is a lack of ammonia rise after forearm exercise testing. The diagnosis may then be confirmed with
604:
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AMPD1 deficiency is caused by a defect in the mechanism for production of AMP deaminase – an enzyme that converts
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intake during vigorous exercise, though this may be offset by increased levels of adenosine, another vasodilator.
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The second effect, the absence of ammonia, is not well understood. It may result in a reduction of the amount of
217:
The cause of cramping is unknown, but may be related to elevated lactate, increased calcium signaling across the
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form of the SNP. In the homozygous form of the mutation, a single genetic base (character) has been changed from
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Tarnopolsky, Mark A.; Parise, Gianni; Gibala, Martin J.; Graham, Terry E.; Rush, James W. E. (15 June 2001).
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MADD lowers aerobic power output, so increased anaerobic power is needed to perform the same amount of work.
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1171:"Myoadenylate deaminase deficiency does not affect muscle anaplerosis during exhaustive exercise in humans"
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decreases alertness and causes sleepiness. In this way, adenosine may play a role in fatigue from MADD.
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84:
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Sabina, R L; Swain, J L; Olanow, C W; Bradley, W G; Fishbein, W N; Dimauro, S; Holmes, E W (1984).
638:"Metabolic Diseases of Muscle - Myoadenylate deaminase deficiency | Muscular Dystrophy Association"
204:
122:) disorder, some researchers have reported the existence of similarly deleterious effects from the
138:– in other words, "C;C" has been replaced by "T;T". A rarer but analogous condition, in which two
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caused by membrane instability from reduced levels of ATP, or increased levels of free adenosine.
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For reasons that are not understood, many people with defective variants of the AMPD genes are
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169:, while others have symptoms including exercise intolerance, and/or muscle pain and cramping.
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Belfrage, Måns; Sollevi, Alf; Segerdahl, Märta; Sjölund, Karl-Fredrik; Hansson, Per (1995).
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1505:"Adenosine and cardioprotection: what can we learn from nature's genetic polymorphism?"
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Symptomatic relief from the effects of MADD may sometimes be achieved by administering
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produced by the muscles, though serum lactate is typically slightly elevated with MADD.
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heavy exercise, so supplementation may be required to rebuild levels of ATP.
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Frost, GS; Brynes, AE; Dhillo, WS; Bloom, SR; McBurney, MI (February 2003).
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The first effect—the loss of AMP—is mostly significant because AMP contains
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Recovery from over-exertion can be hours, days or even months. In cases of
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10.1002/(SICI)1097-4598(199912)22:12<1674::AID-MUS9>3.0.CO;2-0
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1427:"Clinical Use of Creatine in Neuromuscular and Neurometabolic Disorders"
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It is unclear, what, if anything, does it take to unknowingly trigger
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242:
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Morisaki, H; Morisaki, T (2008). "AMPD genes and urate metabolism".
376:. Statements consisting only of original research should be removed.
1130:"Role of nitric oxide in adenosine-induced vasodilation in humans"
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rest, or sitting in a vehicle, must be followed by brisk walking.
291:
1115:"AMPD1 Genotype Predicts Survival in Patients with Heart Failure"
817:
Li, Xinhui; Bantel, Carsten; Conklin, Dawn; Childers, Steven R.;
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bases ("G;G") bases (in the unmutated form) have been changed to
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418:
341:
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102:
In virtually all cases, the deficiency has been caused by an
1433:. Subcellular Biochemistry. Vol. 46. pp. 183–204.
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Mitochondrial neurogastrointestinal encephalopathy syndrome
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the water balance in the body was neutral initially.
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Skalova, K; Luptak, I; Turcani, M; Hulin, I (2002).
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Nihon Rinsho. Japanese
Journal of Clinical Medicine
69:
Adenosine monophosphate deaminase deficiency type 1
40:
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Adenosine monophosphate deaminase deficiency type 1
35:
18:
1431:Creatine and Creatine Kinase in Health and Disease
558:load increment relative to the perceived effort.
302:into cellular energy. In order to use energy, a
79:in which the body consistently lacks the enzyme
27:Metabolic disorder leading to muscle dysfunction
83:, in sufficient quantities. This may result in
1429:. In Salomons, Gajja S.; Wyss, Markus (eds.).
687:"Adenosine monophosphate deaminase deficiency"
632:
630:
1833:Inborn errors of purine-pyrimidine metabolism
1647:
417:, a sugar molecule that is also used to make
286:molecule in the process. It is a part of the
8:
1722:Adenine phosphoribosyltransferase deficiency
249:(muscle weakness) in individuals with MADD.
1220:"Disruption of the Purine Nucleotide Cycle"
326:would be available to the cell through the
1808:Dihydropyrimidine dehydrogenase deficiency
1776:
1743:Purine nucleoside phosphorylase deficiency
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790:"Facts About Metabolic Diseases of Muscle"
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695:United States National Library of Medicine
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392:Learn how and when to remove this message
245:(cholesterol-reducing drugs) will cause
97:myoadenylate deaminase deficiency (MADD)
626:
448:) in the body, reducing blood flow and
440:, and it may result in lower levels of
114:. While it was initially regarded as a
1273:European Journal of Clinical Nutrition
1187:10.1111/j.1469-7793.2001.t01-1-00881.x
322:(ADP), freeing the energy to do work.
252:Anesthesia has the potential to cause
306:converts one of the above fuels into
7:
95:. The disease was formerly known as
1348:Annals of Nutrition and Metabolism
25:
1690:Adenylosuccinate lyase deficiency
1224:Journal of Clinical Investigation
1128:Costa F, Biaggioni I (May 1998).
1070:Journal of Clinical Investigation
996:Molecular Genetics and Metabolism
314:. Cellular processes, especially
45:Myoadenylate deaminase deficiency
840:10.1097/00000542-200404000-00028
754:10.1097/00000539-199510000-00010
346:
241:There is an increased risk that
203:Adenosine mediates pain through
1488:10.1152/japplphysiol.00185.2007
1310:"What is this Adenosine stuff?"
1117:. Japanese Circulation Society.
799:. December 2009. Archived from
1738:Adenosine deaminase deficiency
797:Muscular Dystrophy Association
642:Muscular Dystrophy Association
1:
1476:Journal of Applied Physiology
1425:Tarnopolsky, Mark A. (2007).
1043:10.1016/S0733-8619(05)70184-5
1667:purine–pyrimidine metabolism
1439:10.1007/978-1-4020-6486-9_10
318:, then convert the ATP into
1512:Bratislavske Lekarske Listy
605:Inborn Errors of Metabolism
372:the claims made and adding
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741:Anesthesia & Analgesia
1175:The Journal of Physiology
873:Drug Development Research
134:("T") on both strands of
59:
50:
1314:Australasian Anaesthesia
1147:10.1161/01.HYP.31.5.1061
1384:Klinische Wochenschrift
1286:10.1038/sj.ejcn.1601520
691:Genetics Home Reference
615:Purine Nucleotide Cycle
328:purine nucleotide cycle
276:adenosine monophosphate
237:Potential complications
151:adenosine monophosphate
61:Adenosine monophosphate
1008:10.1006/mgme.2000.3066
308:adenosine triphosphate
254:malignant hyperthermia
219:sarcoplasmic reticulum
1772:Pyrimidine metabolism
1308:Lang, Robert (1998).
320:adenosine diphosphate
280:inosine monophosphate
155:inosine monophosphate
1713:Lesch–Nyhan syndrome
610:Metabolic Myopathies
592:Creatine monohydrate
85:exercise intolerance
670:(23 October 2021).
205:adenosine receptors
106:mutation, known as
1705:Nucleotide salvage
1606:External resources
1396:10.1007/BF01785710
1113:Loh, Evan (2000).
1031:Neurologic Clinics
952:Muscle & Nerve
819:Eisenach, James C.
644:. 18 December 2015
357:possibly contains
282:(IMP), freeing an
161:Symptoms and signs
77:metabolic disorder
1820:
1819:
1816:
1815:
1766:
1765:
1675:Purine metabolism
1629:
1628:
1448:978-1-4020-6485-2
1360:10.1159/000177660
1236:10.1172/JCI109995
1082:10.1172/JCI111265
964:10.1002/mus.20567
885:10.1002/ddr.10170
438:citric acid cycle
436:available to the
402:
401:
394:
359:original research
288:metabolic process
66:
65:
30:Medical condition
16:(Redirected from
1845:
1777:
1680:
1656:
1649:
1642:
1633:
1551:
1541:
1539:
1538:
1532:
1526:. Archived from
1509:
1499:
1461:
1460:
1422:
1416:
1415:
1378:
1372:
1371:
1343:
1337:
1336:
1334:
1333:
1324:. Archived from
1305:
1299:
1298:
1288:
1264:
1258:
1257:
1247:
1230:(6): 1419–1423.
1215:
1209:
1208:
1198:
1166:
1160:
1159:
1149:
1125:
1119:
1118:
1110:
1104:
1103:
1093:
1061:
1055:
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1026:
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984:
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939:
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756:
732:
726:
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705:
699:
698:
683:
672:
663:
654:
653:
651:
649:
634:
404:This failure to
397:
390:
386:
383:
377:
374:inline citations
350:
349:
342:
55:
33:
21:
1853:
1852:
1848:
1847:
1846:
1844:
1843:
1842:
1823:
1822:
1821:
1812:
1796:
1792:Miller syndrome
1787:Orotic aciduria
1762:
1726:
1699:
1669:
1660:
1630:
1625:
1624:
1601:
1600:
1562:
1548:
1536:
1534:
1530:
1507:
1502:
1473:
1470:
1468:Further reading
1465:
1464:
1449:
1424:
1423:
1419:
1390:(24): 1281–90.
1380:
1379:
1375:
1345:
1344:
1340:
1331:
1329:
1307:
1306:
1302:
1266:
1265:
1261:
1217:
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1212:
1168:
1167:
1163:
1127:
1126:
1122:
1112:
1111:
1107:
1063:
1062:
1058:
1028:
1027:
1023:
992:
991:
987:
948:
947:
943:
914:(12): 1674–83.
905:
904:
900:
869:
868:
864:
816:
815:
811:
803:
792:
788:
787:
778:
734:
733:
729:
707:
706:
702:
685:
684:
675:
666:SNPedia, 2019,
664:
657:
647:
645:
636:
635:
628:
623:
601:
577:
569:genetic testing
564:
398:
387:
381:
378:
363:
351:
347:
340:
332:5'-nucleotidase
265:
239:
226:Muscle weakness
212:Muscle cramping
163:
93:muscle cramping
31:
28:
23:
22:
15:
12:
11:
5:
1851:
1849:
1841:
1840:
1835:
1825:
1824:
1818:
1817:
1814:
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1811:
1810:
1804:
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1798:
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1774:
1768:
1767:
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1755:
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1745:
1740:
1734:
1732:
1728:
1727:
1725:
1724:
1719:
1709:
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1701:
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1698:
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1684:
1677:
1671:
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1610:
1609:
1607:
1603:
1602:
1599:
1598:
1587:
1576:
1563:
1558:
1557:
1555:
1554:Classification
1547:
1546:External links
1544:
1543:
1542:
1500:
1469:
1466:
1463:
1462:
1447:
1417:
1373:
1354:(5): 297–302.
1338:
1300:
1259:
1210:
1181:(3): 881–889.
1161:
1120:
1105:
1056:
1021:
985:
941:
898:
879:(4): 350–353.
862:
827:Anesthesiology
809:
806:on 2011-09-27.
776:
727:
700:
673:
655:
625:
624:
622:
619:
618:
617:
612:
607:
600:
597:
576:
573:
563:
560:
509:rhabdomyolysis
461:
460:
453:
430:
400:
399:
354:
352:
345:
339:
336:
310:(ATP) via the
290:that converts
274:that converts
264:
261:
238:
235:
234:
233:
228:
227:
223:
222:
214:
213:
209:
208:
201:
196:
195:
191:
190:
187:rhabdomyolysis
183:
179:
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162:
159:
64:
63:
57:
56:
48:
47:
42:
38:
37:
29:
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
1850:
1839:
1838:Rare diseases
1836:
1834:
1831:
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1828:
1809:
1806:
1805:
1803:
1799:
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1746:
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1736:
1735:
1733:
1729:
1723:
1720:
1718:
1717:Hyperuricemia
1714:
1711:
1710:
1708:
1706:
1702:
1696:
1693:
1691:
1688:
1687:
1685:
1681:
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1582:
1581:
1577:
1574:
1573:
1569:
1565:
1564:
1561:
1556:
1552:
1545:
1533:on 2012-03-23
1529:
1525:
1521:
1518:(6): 187–93.
1517:
1513:
1506:
1501:
1497:
1493:
1489:
1485:
1482:(1): 315–22.
1481:
1477:
1472:
1471:
1467:
1458:
1454:
1450:
1444:
1440:
1436:
1432:
1428:
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1389:
1385:
1377:
1374:
1369:
1365:
1361:
1357:
1353:
1349:
1342:
1339:
1328:on 2011-10-20
1327:
1323:
1319:
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1188:
1184:
1180:
1176:
1172:
1165:
1162:
1157:
1153:
1148:
1143:
1140:(5): 1061–4.
1139:
1135:
1131:
1124:
1121:
1116:
1109:
1106:
1101:
1097:
1092:
1087:
1083:
1079:
1076:(3): 720–30.
1075:
1071:
1067:
1060:
1057:
1052:
1048:
1044:
1040:
1037:(1): 185–94.
1036:
1032:
1025:
1022:
1017:
1013:
1009:
1005:
1002:(1–2): 10–8.
1001:
997:
989:
986:
981:
977:
973:
969:
965:
961:
958:(2): 153–62.
957:
953:
945:
942:
937:
933:
929:
925:
921:
917:
913:
909:
902:
899:
894:
890:
886:
882:
878:
874:
866:
863:
858:
854:
850:
846:
841:
836:
833:(4): 956–61.
832:
828:
824:
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813:
810:
802:
798:
791:
785:
783:
781:
777:
772:
768:
764:
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746:
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738:
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728:
723:
719:
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688:
682:
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603:
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559:
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551:
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541:
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533:
529:
525:
521:
517:
513:
510:
505:
501:
497:
493:
489:
485:
481:
477:
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469:
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458:
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451:
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439:
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416:
412:
411:
410:
407:
396:
393:
385:
382:November 2014
375:
371:
367:
361:
360:
355:This section
353:
344:
343:
337:
335:
333:
329:
323:
321:
317:
313:
309:
305:
301:
297:
293:
289:
285:
281:
277:
273:
269:
268:AMP deaminase
262:
260:
257:
255:
250:
248:
244:
236:
230:
229:
225:
224:
220:
216:
215:
211:
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168:
160:
158:
156:
152:
147:
145:
141:
137:
133:
129:
125:
121:
117:
113:
109:
105:
100:
98:
94:
90:
86:
82:
81:AMP deaminase
78:
75:, is a human
74:
70:
62:
58:
54:
49:
46:
43:
39:
34:
19:
1663:Inborn error
1613:
1589:
1578:
1566:
1535:. Retrieved
1528:the original
1515:
1511:
1479:
1475:
1430:
1420:
1387:
1383:
1376:
1351:
1347:
1341:
1330:. Retrieved
1326:the original
1313:
1303:
1279:(2): 293–8.
1276:
1272:
1262:
1227:
1223:
1213:
1178:
1174:
1164:
1137:
1134:Hypertension
1133:
1123:
1108:
1073:
1069:
1059:
1034:
1030:
1024:
999:
995:
988:
955:
951:
944:
911:
908:Muscle Nerve
907:
901:
876:
872:
865:
830:
826:
812:
801:the original
747:(4): 713–7.
744:
740:
730:
716:(4): 771–7.
713:
709:
703:
697:. July 2008.
690:
667:
646:. Retrieved
590:
582:
578:
565:
556:
552:
549:
546:
542:
538:
534:
530:
526:
522:
518:
514:
506:
502:
498:
494:
490:
486:
482:
478:
474:
470:
466:
464:by default.
462:
442:nitric oxide
403:
388:
379:
356:
324:
312:mitochondria
266:
258:
251:
240:
167:asymptomatic
164:
148:
136:Chromosome 1
124:heterozygous
111:
107:
101:
96:
72:
68:
67:
44:
1748:Xanthinuria
457:lactic acid
446:vasodilator
425:, and some
194:Muscle pain
118:(or purely
89:muscle pain
41:Other names
1827:Categories
1801:Catabolism
1731:Catabolism
1537:2011-08-12
1332:2011-08-14
668:rs17602729
621:References
366:improve it
120:homozygous
108:rs17602729
1780:Anabolism
1683:Anabolism
1322:1032-2515
575:Treatment
562:Diagnosis
406:deaminate
370:verifying
338:Mechanism
278:(AMP) to
153:(AMP) to
130:("C") to
116:recessive
1615:Orphanet
1524:12448564
1496:17463303
1457:18652078
1412:35397362
1295:12571662
1205:11410643
1051:10658174
1016:11001791
980:22609911
972:16671104
936:41846255
928:10567080
893:84898432
857:35764254
849:15087633
821:(2004).
771:23963005
722:18409530
599:See also
434:fumarate
247:myopathy
200:painful.
128:cytosine
1596:C538234
1575:: G71.3
1404:3102830
1368:1776826
1254:7440723
1196:2278656
1156:9576114
1100:6707201
763:7573999
648:10 June
427:enzymes
364:Please
316:muscles
300:protein
284:ammonia
232:damage.
173:Fatigue
144:adenine
140:guanine
132:thymine
1585:102770
1522:
1494:
1455:
1445:
1410:
1402:
1366:
1320:
1293:
1252:
1245:371628
1242:
1203:
1193:
1154:
1098:
1091:425074
1088:
1049:
1014:
978:
970:
934:
926:
891:
855:
847:
769:
761:
720:
585:ribose
450:oxygen
415:ribose
298:, and
272:enzyme
270:is an
263:Causes
243:statin
1531:(PDF)
1508:(PDF)
1408:S2CID
976:S2CID
932:S2CID
889:S2CID
853:S2CID
804:(PDF)
793:(PDF)
767:S2CID
292:sugar
73:AMPD1
1753:Gout
1665:of
1591:MeSH
1580:OMIM
1520:PMID
1492:PMID
1453:PMID
1443:ISBN
1400:PMID
1364:PMID
1318:ISSN
1291:PMID
1250:PMID
1201:PMID
1152:PMID
1096:PMID
1047:PMID
1012:PMID
968:PMID
924:PMID
845:PMID
759:PMID
718:PMID
650:2017
304:cell
112:C34T
91:and
1568:ICD
1516:103
1484:doi
1480:103
1435:doi
1392:doi
1356:doi
1281:doi
1240:PMC
1232:doi
1191:PMC
1183:doi
1179:533
1142:doi
1086:PMC
1078:doi
1039:doi
1004:doi
960:doi
916:doi
881:doi
835:doi
831:100
749:doi
444:(a
423:RNA
419:DNA
368:by
296:fat
110:or
104:SNP
71:or
1829::
1620:45
1618::
1594::
1583::
1572:10
1514:.
1510:.
1490:.
1478:.
1451:.
1441:.
1406:.
1398:.
1388:64
1386:.
1362:.
1352:35
1350:.
1316:.
1312:.
1289:.
1277:57
1275:.
1271:.
1248:.
1238:.
1228:66
1226:.
1222:.
1199:.
1189:.
1177:.
1173:.
1150:.
1138:31
1136:.
1132:.
1094:.
1084:.
1074:73
1072:.
1068:.
1045:.
1035:18
1033:.
1010:.
1000:71
998:.
974:.
966:.
956:34
954:.
930:.
922:.
912:22
910:.
887:.
877:58
875:.
851:.
843:.
829:.
825:.
795:.
779:^
765:.
757:.
745:81
743:.
739:.
714:66
712:.
693:.
689:.
676:^
658:^
640:.
629:^
571:.
421:,
294:,
99:.
87:,
1715:/
1655:e
1648:t
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1570:-
1560:D
1540:.
1498:.
1486::
1459:.
1437::
1414:.
1394::
1370:.
1358::
1335:.
1297:.
1283::
1256:.
1234::
1207:.
1185::
1158:.
1144::
1102:.
1080::
1053:.
1041::
1018:.
1006::
982:.
962::
938:.
918::
895:.
883::
859:.
837::
773:.
751::
724:.
652:.
395:)
389:(
384:)
380:(
362:.
20:)
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
